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Acta Cryst. (2010). E66, o1274
https://doi.org/10.1107/S1600536810014996
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N-Benzyl-2-(2-bromo­phen­yl)-2-(2-nitro­phen­oxy)acetamide

H. M. Li and J.-L. Wu
The title compound, C21H17BrN2O4, a 2-phen­oxy-2-phenyl­acetamide derivative, exhibits a stereogenic center but crystallizes as a racemate as indicated by the centrosymmetric space group. In the mol­ecular structure, the nitro-substituted benzene ring is coplanar [dihedral angle = 12.9 (1)°] with the plane formed by H—N—C(=O)—C=O due to intra­molecular N—H...O hydrogen-bond inter­actions.
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Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536810014996/im2196sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536810014996/im2196Isup2.hkl
Contains datablock I

CCDC reference: 781276

checkCIF report

Key indicators

  • Single-crystal X-ray study
  • T = 293 K
  • Mean [sigma](C-C) = 0.006 Å
  • R factor = 0.038
  • wR factor = 0.105
  • Data-to-parameter ratio = 13.2

checkCIF/PLATON results

No syntax errors found




Alert level C
PLAT241_ALERT_2_C Check High      Ueq as Compared to Neighbors for         C7
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for        N23
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for         C6
PLAT331_ALERT_2_C Small Average Phenyl   C-C Dist. C1     -C6            1.37 Ang.
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.595         23


Alert level G
PLAT154_ALERT_1_G The su's on the Cell Angles are Equal  (x 10000)        600 Deg.
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported   _diffrn_ambient_temperature        293 K
PLAT793_ALERT_4_G The Model has Chirality at C9      (Verify) ....          S


   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   5 ALERT level C = Check and explain
   4 ALERT level G = General alerts; check

   3 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   4 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check
Comment top

The title compound, C21H17BrN2O4, is a 2-phenoxy-2-phenyl-acetamide derivative, which have been reported to deliver various biological activities such as acting as inhibitors of the coagulation factors Xa and IXa and are therefore used for the therapy of thromboembolic disorder and as safe and effective anticoagulants for myocardial infarction and ischemic disease (Dorsch, et al.; 2002, Wang et al., 2010). They are also active as glucokinase activators rendering their use for the treatment of type I and type II diabetes (Lau, et al.; 2003).

The title compound has recently been obtained during the Lewis base-catalyzed phenol-Passerini three-component reaction (phenol-P-3CR) from nitrophenols, aryl aldehydes and alkyl isocyanides (Dai & Li; 2007). We report here its crystal structure. In the molecular structure (Fig. 1), there is one benzyl group linked to the amide nitrogen atom. In addition, one 2-bromobenzene and a 2-nitrophenoxy substituents are attached to the α-carbon. The nitro-substituted benzene moiety is coplanar with the plane formed by atoms H22-N22-C8-C9-O2 due to intramolecular hydrogen bond interactions between N22-H22···O2 and N22-H22···O25.

Related literature top

For the synthesis and biological activity of 2-phenoxy-2-phenyl-acetamides, see: Dorsch et al. (2002); Wang et al. (2010); Lau et al. (2003). For additional synthetic procedures, see: Dai & Li (2007).

Experimental top

To a solution of 2-nitrophenol (28 mg, 0.20 mmol) in anhydrous MeCN (0.2 mL, 1.0 M) in a 2-mL tube were added 2-bromobenzaldehyde (48.0 mg, 0.26 mmol), N,N-diisopropylethylamine (0.004 mL, 0.02 mmol, 10 mol%), and benzyl isocyanide (0.037 mL, 0.30 mmol, 1.5 equiv). The resulting mixture was stirred at 352 K under a nitrogen atmosphere for 72 h. The reaction mixture was concentrated under reduced pressure and the residue was then puried by flash column chromatography (silica gel, eluted with 20% EtOAc in light petroleum ether) to afford the title compound as a yellow solid (84.0 mg, 95%). mp 418-419 K (EtOAc-hexane). Single crystals suitable for X-ray diffraction of the title compound were grown in the mixed solvent of EtOAc and hexane (v:v = 1:3) at 283 K.

Refinement top

The H atoms were placed in calculated positions with C—H = 0.93-0.98 Å, and included in the refinement in riding model, with Uiso(H) = 1.2Ueq (carrier atom).

Structure description top

The title compound, C21H17BrN2O4, is a 2-phenoxy-2-phenyl-acetamide derivative, which have been reported to deliver various biological activities such as acting as inhibitors of the coagulation factors Xa and IXa and are therefore used for the therapy of thromboembolic disorder and as safe and effective anticoagulants for myocardial infarction and ischemic disease (Dorsch, et al.; 2002, Wang et al., 2010). They are also active as glucokinase activators rendering their use for the treatment of type I and type II diabetes (Lau, et al.; 2003).

The title compound has recently been obtained during the Lewis base-catalyzed phenol-Passerini three-component reaction (phenol-P-3CR) from nitrophenols, aryl aldehydes and alkyl isocyanides (Dai & Li; 2007). We report here its crystal structure. In the molecular structure (Fig. 1), there is one benzyl group linked to the amide nitrogen atom. In addition, one 2-bromobenzene and a 2-nitrophenoxy substituents are attached to the α-carbon. The nitro-substituted benzene moiety is coplanar with the plane formed by atoms H22-N22-C8-C9-O2 due to intramolecular hydrogen bond interactions between N22-H22···O2 and N22-H22···O25.

For the synthesis and biological activity of 2-phenoxy-2-phenyl-acetamides, see: Dorsch et al. (2002); Wang et al. (2010); Lau et al. (2003). For additional synthetic procedures, see: Dai & Li (2007).

Computing details top

Data collection: CrysAlis PRO (Oxford Diffraction, 2009); cell refinement: CrysAlis PRO (Oxford Diffraction, 2009); data reduction: CrysAlis PRO (Oxford Diffraction, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures top
[Figure 1] Fig. 1. Molecular structure of (1). Displacement ellipsoids are drawn at the 40% probability level and H atoms are shown as small circles of arbitary radii.
N-Benzyl-2-(2-bromophenyl)-2-(2-nitrophenoxy)acetamide top
Crystal data top
C21H17BrN2O4Z = 2
Mr = 441.28F(000) = 448
Triclinic, P1Dx = 1.524 Mg m−3
Hall symbol: -P 1Cu Kα radiation, λ = 1.54184 Å
a = 7.5818 (5) ÅCell parameters from 3052 reflections
b = 10.4650 (7) Åθ = 3.5–66.9°
c = 13.1095 (10) ŵ = 3.17 mm−1
α = 73.939 (6)°T = 293 K
β = 82.878 (6)°Block, colorless
γ = 74.447 (6)°0.38 × 0.26 × 0.18 mm
V = 961.56 (12) Å3
Data collection top
Oxford Diffraction Xcalibur Atlas Gemini ultra
diffractometer		3363 independent reflections
Radiation source: fine-focus sealed tube2522 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.030
Detector resolution: 10.3592 pixels mm-1θmax = 66.6°, θmin = 3.5°
ω scansh = −9→8
Absorption correction: multi-scan
(CrysAlis PRO; Oxford Diffraction, 2009)		k = −11→12
Tmin = 0.427, Tmax = 0.565l = −15→15
7135 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.038H-atom parameters constrained
wR(F2) = 0.105 w = 1/[σ2(Fo2) + (0.0523P)2 + 0.350P]
where P = (Fo2 + 2Fc2)/3
S = 1.03(Δ/σ)max < 0.001
3363 reflectionsΔρmax = 0.37 e Å−3
254 parametersΔρmin = −0.39 e Å−3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0258 (10)
Crystal data top
C21H17BrN2O4γ = 74.447 (6)°
Mr = 441.28V = 961.56 (12) Å3
Triclinic, P1Z = 2
a = 7.5818 (5) ÅCu Kα radiation
b = 10.4650 (7) ŵ = 3.17 mm−1
c = 13.1095 (10) ÅT = 293 K
α = 73.939 (6)°0.38 × 0.26 × 0.18 mm
β = 82.878 (6)°
Data collection top
Oxford Diffraction Xcalibur Atlas Gemini ultra
diffractometer		3363 independent reflections
Absorption correction: multi-scan
(CrysAlis PRO; Oxford Diffraction, 2009)		2522 reflections with I > 2σ(I)
Tmin = 0.427, Tmax = 0.565Rint = 0.030
7135 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0380 restraints
wR(F2) = 0.105H-atom parameters constrained
S = 1.03Δρmax = 0.37 e Å−3
3363 reflectionsΔρmin = −0.39 e Å−3
254 parameters
Special details top

Experimental. (CrysAlis Pro; Oxford Diffraction, 2009) Version 1.171.33.53 (release 17-11-2009 CrysAlis171 .NET) (compiled Nov 17 2009,16:58:22) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Br270.67572 (5)0.56595 (4)0.87665 (3)0.0848 (2)
O20.3651 (3)0.99683 (19)0.82814 (14)0.0599 (5)
O240.6787 (3)0.8846 (3)0.63093 (18)0.0856 (7)
O250.2519 (5)1.2538 (2)0.8109 (2)0.1010 (9)
O260.0566 (5)1.3176 (3)0.9264 (3)0.1318 (13)
N220.5004 (4)1.0913 (3)0.64616 (19)0.0712 (7)
H220.41531.13180.68460.085*
N230.1698 (4)1.2288 (3)0.8964 (2)0.0653 (7)
C10.6438 (6)1.3641 (4)0.5979 (3)0.0878 (11)
H10.51901.40280.60640.105*
C20.7724 (10)1.4280 (5)0.6178 (3)0.1174 (18)
H20.73411.50900.63950.141*
C30.9541 (11)1.3690 (8)0.6046 (4)0.126 (2)
H31.04011.41010.61820.152*
C41.0118 (7)1.2529 (7)0.5724 (4)0.1164 (18)
H41.13651.21500.56280.140*
C50.8863 (5)1.1907 (4)0.5537 (3)0.0829 (10)
H50.92671.10980.53200.099*
C60.7016 (4)1.2457 (4)0.5664 (2)0.0629 (8)
C70.5676 (6)1.1746 (5)0.5464 (3)0.0911 (13)
H7B0.46461.24240.51080.109*
H7A0.62591.11590.49980.109*
C80.5655 (4)0.9562 (4)0.6794 (2)0.0615 (8)
C90.4855 (4)0.8876 (3)0.7880 (2)0.0515 (6)
H90.58490.83960.83630.062*
C100.3835 (4)0.7874 (3)0.7772 (2)0.0477 (6)
C110.4463 (4)0.6461 (3)0.8127 (2)0.0577 (7)
C120.3448 (5)0.5585 (3)0.8030 (3)0.0745 (9)
H120.38960.46420.82710.089*
C130.1799 (5)0.6103 (4)0.7584 (3)0.0750 (9)
H130.11100.55110.75320.090*
C140.1141 (4)0.7491 (4)0.7209 (2)0.0673 (8)
H140.00170.78420.68950.081*
C150.2163 (4)0.8368 (3)0.7301 (2)0.0558 (7)
H150.17160.93090.70400.067*
C160.3115 (4)0.9775 (3)0.93255 (19)0.0460 (6)
C170.3463 (4)0.8503 (3)1.0060 (2)0.0544 (7)
H170.41340.77280.98460.065*
C180.2821 (4)0.8388 (3)1.1098 (2)0.0631 (8)
H180.30770.75341.15830.076*
C190.1805 (4)0.9514 (4)1.1434 (2)0.0698 (9)
H190.13730.94201.21400.084*
C200.1435 (4)1.0772 (3)1.0723 (2)0.0628 (8)
H200.07391.15371.09430.075*
C210.2096 (4)1.0908 (3)0.9674 (2)0.0488 (6)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br270.0661 (3)0.0668 (3)0.1161 (4)0.00496 (17)−0.0286 (2)−0.0247 (2)
O20.0875 (14)0.0447 (10)0.0454 (10)−0.0160 (10)0.0037 (9)−0.0113 (8)
O240.0676 (14)0.124 (2)0.0680 (14)−0.0247 (14)0.0139 (12)−0.0354 (14)
O250.165 (3)0.0495 (13)0.0740 (16)−0.0125 (15)−0.0038 (18)−0.0060 (12)
O260.135 (3)0.0565 (16)0.171 (3)0.0045 (17)0.036 (2)−0.0219 (18)
N220.0792 (18)0.085 (2)0.0506 (14)−0.0405 (16)0.0013 (13)−0.0016 (13)
N230.0701 (16)0.0466 (14)0.084 (2)−0.0138 (13)−0.0136 (14)−0.0209 (13)
C10.103 (3)0.087 (3)0.062 (2)−0.022 (2)0.0102 (19)−0.0068 (19)
C20.201 (6)0.094 (3)0.068 (3)−0.065 (4)0.000 (3)−0.015 (2)
C30.175 (6)0.149 (5)0.083 (3)−0.113 (5)−0.031 (4)0.009 (3)
C40.085 (3)0.156 (5)0.099 (3)−0.057 (3)−0.020 (2)0.014 (3)
C50.081 (2)0.089 (3)0.069 (2)−0.025 (2)−0.0016 (18)−0.0021 (18)
C60.071 (2)0.078 (2)0.0367 (14)−0.0313 (17)−0.0043 (13)0.0037 (14)
C70.104 (3)0.126 (3)0.0500 (18)−0.070 (3)−0.0088 (18)0.0084 (19)
C80.0524 (17)0.088 (2)0.0523 (17)−0.0299 (17)−0.0051 (14)−0.0172 (16)
C90.0577 (16)0.0545 (15)0.0455 (14)−0.0160 (13)−0.0042 (12)−0.0152 (12)
C100.0467 (14)0.0546 (15)0.0455 (14)−0.0130 (12)0.0004 (11)−0.0192 (12)
C110.0501 (15)0.0574 (17)0.0684 (18)−0.0065 (13)−0.0058 (13)−0.0256 (14)
C120.077 (2)0.0560 (18)0.100 (3)−0.0164 (16)−0.0095 (19)−0.0330 (17)
C130.075 (2)0.079 (2)0.088 (2)−0.0344 (19)−0.0033 (18)−0.0341 (19)
C140.0490 (16)0.098 (3)0.0607 (18)−0.0223 (17)−0.0044 (14)−0.0242 (17)
C150.0513 (15)0.0632 (17)0.0507 (15)−0.0112 (14)−0.0016 (12)−0.0142 (13)
C160.0512 (14)0.0500 (14)0.0443 (14)−0.0208 (12)−0.0049 (11)−0.0148 (11)
C170.0654 (17)0.0504 (15)0.0479 (15)−0.0143 (13)−0.0077 (13)−0.0114 (12)
C180.0674 (19)0.071 (2)0.0466 (16)−0.0188 (16)−0.0079 (14)−0.0045 (14)
C190.0681 (19)0.094 (3)0.0481 (16)−0.0191 (18)−0.0003 (14)−0.0220 (17)
C200.0556 (17)0.075 (2)0.0663 (19)−0.0107 (15)−0.0044 (14)−0.0361 (16)
C210.0486 (14)0.0482 (14)0.0561 (16)−0.0161 (12)−0.0107 (12)−0.0165 (12)
Geometric parameters (Å, º) top
Br27—C111.903 (3)C8—C91.538 (4)
O2—C161.354 (3)C9—C101.504 (4)
O2—C91.439 (3)C9—H90.9800
O24—C81.218 (4)C10—C151.386 (4)
O25—N231.209 (4)C10—C111.388 (4)
O26—N231.203 (4)C11—C121.384 (4)
N22—C81.331 (4)C12—C131.357 (5)
N22—C71.473 (4)C12—H120.9300
N22—H220.8600C13—C141.370 (5)
N23—C211.461 (4)C13—H130.9300
C1—C61.358 (5)C14—C151.387 (4)
C1—C21.406 (7)C14—H140.9300
C1—H10.9300C15—H150.9300
C2—C31.361 (8)C16—C171.391 (4)
C2—H20.9300C16—C211.391 (4)
C3—C41.341 (8)C17—C181.371 (4)
C3—H30.9300C17—H170.9300
C4—C51.367 (6)C18—C191.375 (5)
C4—H40.9300C18—H180.9300
C5—C61.372 (5)C19—C201.367 (5)
C5—H50.9300C19—H190.9300
C6—C71.494 (5)C20—C211.386 (4)
C7—H7B0.9700C20—H200.9300
C7—H7A0.9700
C16—O2—C9121.1 (2)C10—C9—H9109.5
C8—N22—C7122.8 (3)C8—C9—H9109.5
C8—N22—H22118.6C15—C10—C11117.2 (3)
C7—N22—H22118.6C15—C10—C9119.1 (3)
O26—N23—O25120.9 (3)C11—C10—C9123.7 (2)
O26—N23—C21118.1 (3)C12—C11—C10121.3 (3)
O25—N23—C21120.9 (3)C12—C11—Br27117.6 (2)
C6—C1—C2120.0 (4)C10—C11—Br27121.0 (2)
C6—C1—H1120.0C13—C12—C11120.1 (3)
C2—C1—H1120.0C13—C12—H12120.0
C3—C2—C1118.7 (5)C11—C12—H12120.0
C3—C2—H2120.7C12—C13—C14120.4 (3)
C1—C2—H2120.7C12—C13—H13119.8
C4—C3—C2121.5 (5)C14—C13—H13119.8
C4—C3—H3119.3C13—C14—C15119.5 (3)
C2—C3—H3119.3C13—C14—H14120.2
C3—C4—C5119.6 (5)C15—C14—H14120.2
C3—C4—H4120.2C10—C15—C14121.5 (3)
C5—C4—H4120.2C10—C15—H15119.3
C4—C5—C6121.1 (5)C14—C15—H15119.3
C4—C5—H5119.4O2—C16—C17123.9 (2)
C6—C5—H5119.4O2—C16—C21117.9 (2)
C1—C6—C5119.1 (4)C17—C16—C21118.2 (2)
C1—C6—C7121.0 (4)C18—C17—C16120.2 (3)
C5—C6—C7119.9 (4)C18—C17—H17119.9
N22—C7—C6111.5 (3)C16—C17—H17119.9
N22—C7—H7B109.3C17—C18—C19121.2 (3)
C6—C7—H7B109.3C17—C18—H18119.4
N22—C7—H7A109.3C19—C18—H18119.4
C6—C7—H7A109.3C20—C19—C18119.5 (3)
H7B—C7—H7A108.0C20—C19—H19120.2
O24—C8—N22125.8 (3)C18—C19—H19120.2
O24—C8—C9118.7 (3)C19—C20—C21120.0 (3)
N22—C8—C9115.5 (3)C19—C20—H20120.0
O2—C9—C10111.1 (2)C21—C20—H20120.0
O2—C9—C8106.1 (2)C20—C21—C16120.9 (3)
C10—C9—C8111.0 (2)C20—C21—N23117.2 (3)
O2—C9—H9109.5C16—C21—N23121.9 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N22—H22···O20.862.082.521 (3)111
N22—H22···O250.862.393.227 (4)164

Experimental details

Crystal data
Chemical formulaC21H17BrN2O4
Mr441.28
Crystal system, space groupTriclinic, P1
Temperature (K)293
a, b, c (Å)7.5818 (5), 10.4650 (7), 13.1095 (10)
α, β, γ (°)73.939 (6), 82.878 (6), 74.447 (6)
V (Å3)961.56 (12)
Z2
Radiation typeCu Kα
µ (mm−1)3.17
Crystal size (mm)0.38 × 0.26 × 0.18
Data collection
DiffractometerOxford Diffraction Xcalibur Atlas Gemini ultra
Absorption correctionMulti-scan
(CrysAlis PRO; Oxford Diffraction, 2009)
Tmin, Tmax0.427, 0.565
No. of measured, independent and
observed [I > 2σ(I)] reflections		7135, 3363, 2522
Rint0.030
(sin θ/λ)max (Å−1)0.595
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.038, 0.105, 1.03
No. of reflections3363
No. of parameters254
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.37, −0.39

Computer programs: CrysAlis PRO (Oxford Diffraction, 2009), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N22—H22···O20.862.082.521 (3)111
N22—H22···O250.862.393.227 (4)164
 

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